Clostridium difficile-specific antibodies and uses thereof

• US 9,771,416 B2
• Filed: 10/25/2011
• Issued: 09/26/2017
• Est. Priority Date: 10/25/2010
• Status: Active Grant

• Current Assignee: National Research Council Canada
• Original Assignee: National Research Council Canada
• Inventors: Hussack, Greg, Arbabi-Ghahroudi, Mehdi Nath, Mackenzie, Roger, Tanha, Jamshid
• Primary Examiner(s): Zeman, Robert A
• Application Number:
  US13/881,398
• Publication Number:
  US 20130230537A1
• Time in Patent Office: 2,163 Days
• Field of Search: None
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: C07K 16/1282 from Clostridium (G)
• CPC Class Codes: C07K 2317/22 from camelids, e.g. camel, llama or dromedary
• CPC Class Codes: C07K 2317/35 Valency
• CPC Class Codes: C07K 2317/569 Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody®
• CPC Class Codes: C07K 2317/76 Antagonist effect on antigen, e.g. neutralization or inhibition of binding
• CPC Class Codes: C07K 2317/92 Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
• CPC Class Codes: C07K 2317/94 Stability, e.g. half-life, pH, temperature or enzyme-resistance
• CPC Class Codes: G01N 2333/33 from Clostridium (G)
• CPC Class Codes: G01N 33/56911 Bacteria

Abstract

The present invention is directed to Clostridium difficile toxin-specific antibodies, compositions, and uses thereof. The anti-toxin antibodies may be specific for either TcdA or TcdB. The invention also includes methods of treating a Clostridium difficile infection, methods of capturing Clostridium difficile toxins, and methods of detecting Clostridium difficile toxins.

Claims

1. An isolated or purified single domain antibody, comprising a sequence of CDR 1 of GRTFSMYR (SEQ ID NO:

2);

CDR2 of ITRNGSST (SEQ ID NO;

8); and

CDR3 of AATSGSSYLDAAHVYDY (SEQ ID NO;

14).

2. The isolated or purified single domain antibody of claim 1, comprising a sequence selected from the group consisting of:

3. A multivalent polypeptide comprising at least one of the isolated or purified single domain antibody of claim 1.

4. The isolated or purified single domain antibody of claim 1, wherein the antibody is immobilized onto a surface.

5. The isolated or purified single domain antibody of claim 1, wherein the antibody is linked to a cargo molecule.

6. The isolated or purified single domain antibody of claim 5, wherein the cargo molecule is a detectable agent, a therapeutic, a drug, a peptide, a carbohydrate moiety, an enzyme, or a cytotoxic agent;

one or more liposomes loaded with a detectable agent, a therapeutic, a drug, a peptide, an enzyme, or a cytotoxic agent;

or one or more nanoparticle, nanowire, nanotube, or quantum dots.

7. A composition comprising one or more than one of the isolated or purified single domain antibody of claim 1 and a pharmaceutically-acceptable carrier, diluent, or excipient.

8. A method of treating a Clostridium difficile infection, comprising administering isolated or purified single domain antibody, comprising a sequence selected from the group consisting of:

9. A method of detecting Clostridium difficile toxins comprising contacting a sample with an isolated or purified single domain antibody comprising a sequence selected from the group consisting of